The multifunctional GIT family of proteins

203Citations
Citations of this article
142Readers
Mendeley users who have this article in their library.

Abstract

The G-protein-coupled receptor (GPCR)-kinase-interacting proteins 1 and 2 (GIT1 and GIT2) are ubiquitous multidomain proteins involved in diverse cellular processes. They traffic between three distinct cellular compartments (cytoplasmic complexes, focal adhesions and the cell periphery) through interactions with proteins including ARF, Rac1 and Cdc42 GTPases, p21-activated kinase (PAK), PAK-interacting exchange factor (PIX), the kinase MEK1, phospholipase Cγ (PLCγ) and paxillin. GITs and PIX cooperate to form large oligomeric complexes to which other proteins are transiently recruited. Activation of Rac1 and Cdc42 drives association of PAK with these oligomers, which unmasks the paxillin-binding site in GITs that recruits them to focal complexes. Th ere, they regulate cytoskeletal dynamics by feedback inhibition of Rac1. GITs also participate in receptor internalization by regulating membrane trafficking between the plasma membrane and endosomes, targeting ARF GTPases through their ARF GTPase-activating protein (ARF-GAP) activity. Furthermore, GITs act as scaffolds to control spatial activation of several signaling molecules. Finally, recent results suggest pathogenic roles for GIT proteins in Huntington's disease and HIV infection.

Cite

CITATION STYLE

APA

Hoefen, R. J., & Berk, B. C. (2006, April 15). The multifunctional GIT family of proteins. Journal of Cell Science. https://doi.org/10.1242/jcs.02925

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free